title: Regulation of advanced therapy medicinal products in Europe and the role of academia.
abstract: OBJECTIVE
  Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them.
  
  
  METHODS
  European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented.
  
  
  RESULTS
  Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS.
  
  
  CONCLUSIONS
  GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field.
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: Kim F
authors.initials: KF
authors.lastname: Pearce
authors.affiliation: TUMCells Interdisciplinary Centre for Cellular Therapies, Technical University Munich, Faculty of Medicine, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hildebrandt
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.affiliation: Lund University, Stem Cell Center, Lund, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
authors.affiliation: Institute of Cellular Therapeutics, IFB-Tx, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Worel
authors.affiliation: Department of Haematology, Imperial College London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Apperley
authors.affiliation: University Hospital, Regensburg, Germany.
authors.forename: Matthius
authors.initials: M
authors.lastname: Edinger
authors.affiliation: University Hospital, Regensburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hauser
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Mischak-Weissinger
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.affiliation: Department of Haematology, Royal Free Hospital & University College London, United Kingdom. Electronic address: m.lowdell@ucl.ac.uk.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lowdell
mesh_terms: D000046:Academic Medical Centers / Q000706:statistics & numerical data*; D000818:Animals; D001709:Biotechnology; D064987:Cell- and Tissue-Based Therapy; D003132:Commerce; D005062:European Union; D015316:Genetic Therapy / Q000331:legislation & jurisprudence*; D033161:Government Regulation; D019983:Guideline Adherence / Q000706:statistics & numerical data*; D006801:Humans; D057170:Translational Research, Biomedical / Q000706:statistics & numerical data*
keywords: European Union; advanced therapy medicinal products; good manufacturing practice; manufacturing; regulation